GDB domain and disrupts the DAD-DID-interaction thus promoting actin assembly. But this requires high concentrations of Rho-GTP, which may be not physiological. Hence, the release of mDia1 from autoinhibition seems to require nonspecific membrane-associated factors that cooperate with Rho-GTP. Several binding proteins can regulate mDia1 localization and activity: ABI1: Helps to localize mDia1 to lamellipodia, filopodia and cell adhesions CLIP 170: Binds the FH2 domain and recruits mDia1 to sites of phagocytosis Gα12/13: Helps to localize mDia1 to the leading edge of migrating cells RhoA: Required for mDia1 localization to adherens junctions and partially removes mDia's autoinhibition RhoB: Helps to localize mDia1 to endosomes Furthermore the scaffold protein (IQGAP1) seems to impact on mDia1. IQGAP1 regulates the localization of mDia1 to the leading edge to cells. The only tested short C-terminal fragment of IQGAP1 (aa 1503 to 1657) was not activating the mDia1 actin polymerization activity in vitro. However expression of this fragment in macrophages reduced phagocytosis. Thus it remains open if IQGAP1 influences the activity of mDia1 directly like it does for NWASP. Mechanism Nucleation In contrast to the Arp 2/3 complex, formins nucleate the formation of unbranched actin filaments. FH2 domains lack structural similarity to actin but can bind actin monomers with very weak affinity. The FH2 dimer nucleates filament assembly by interacting directly with and stabilizing actin polymerization intermediates (dimers and trimers). Elongation A formin dimer remains constantly bound to the plus end of an actin filament despite ongoing polymerization. One formin of a dimer dissociates from the barbed end to take the next step while the second formin of the dimer remains bound. Thus the formin dimer processively adds actin monomers to the barbed end and are constantly present at the barbed end of an actin filament (processive capping). The FH1 domain recruits actin monomers through profilin binding, but it does not promote nucleation. Studies demonstrated that FH2 domains protect the rapidly elongating barbed ends of filaments from the vast molar excesses of actin capping proteins. The precise mechanisms of actin filament nucleation remains an area of active investigation. The rate of FH2 movement while elongation on an actin filament matches the rate of actin subunit addition, which can exceed 100 subunits per second. Profilin as a ubiquitous actin-binding protein is associated with most actin monomers in cells. Interactions between profilin-actin with the FH1 domain can accelerate the elongation at the FH2-capped barbed ends. Function The